Pathway in MS May Drive Treatment Outcome

Although interferon-β (IFN-β) is used to reduce the number and severity of relapses in patients with relapsing remitting multiple sclerosis (RRMS), a frustration for both patients and physicians is that the treatment is more effective in some patients than others. Studies by researchers at Stanford University and colleagues have now suggested that there may be two distinct versions of multiple sclerosis and that the effectiveness of β-interferon may depend on the type of disease that the patient has.

The team found that superficially similar experimental autoimmune encephalitis (EAE), an animal model of multiple sclerosis, can be induced either by T helper type 1 (TH1) cells or by TH17 cells. IFN-β was effective in treating TH1-induced EAE but exacerbated disease caused by TH17 cells. In TH1-induced EAE, treatment was accompanied by increased interleukin-10 (IL-10) production whereas in TH17-induced EAE, IL-10 levels were unaffected by treatment, although IL-17 levels were reduced. Both induction of IL-10 production and suppression of IL-17 levels were dependent on IFN-γ; in the absence of IFN-γ signalling, IFN-β did not reduce the symptoms of EAE.

The team then measured IL-17 levels in blood samples from 26 RRMS patients taken before and about 2 years after starting treatment with IFN-β. When treatment responses were matched to IL-17 levels a clear pattern emerged: patients with a good response had very low levels of the IL-17 family member, IL-17F, whereas those who responded poorly – about 30% of the patients – had high levels of IL-17F. Although the team caution that the results need to be confirmed in larger groups of patients, the study has the potential to transform treatment for MS by stratifying patients into likely IFN-β responders and non-responders. Eventually, a simple blood test could improve the response rate to IFN-β and spare non-responders from the known flu-like side effects of a treatment that could even worsen their disease.